Objectives: While electronic health record (EHR) systems have potential to drive improvements in healthcare, a majority of EHR implementations fall short of expectations. Shortcomings in implementations are often due to organizational issues around the implementation process rather than technological problems. Evidence from both the information technology and healthcare management literature can be applied to improve the likelihood of implementation success, but the translation of this evidence into practice has not been widespread. Our objective was to comprehensively study and synthesize best practices for managing ambulatory EHR system implementation in healthcare organizations, highlighting applicable management theories and successful strategies. Methods: We held 45 interviews with key informants in six U.S. healthcare organizations purposively selected based on reported success with ambulatory EHR implementation. We also conducted six focus groups comprised of 37 physicians. Interview and focus group transcripts were analyzed using both deductive and inductive methods to answer research questions and explore emergent themes. Results: We suggest that successful management of ambulatory EHR implementation can be guided by the Plan-Do-Study-Act (PDSA) quality improvement (QI) model. While participants did not acknowledge nor emphasize use of this model, we found evidence that successful implementation practices could be framed using the PDSA model. Additionally, successful sites had three strategies in common: 1) use of evidence from published health information technology (HIT) literature emphasizing implementation facilitators; 2) focusing on workflow; and 3) incorporating critical management factors that facilitate implementation. Conclusions: Organizations seeking to improve ambulatory EHR implementation processes can use frameworks such as the PDSA QI model to guide efforts and provide a means to formally accommodate new evidence over time. Implementing formal management strategies and incorporating new evidence through the PDSA model is a key element of evidence-based management and a crucial way for organizations to position themselves to proactively address implementation and use challenges before they are exacerbated. (C) 2014 Elsevier Ireland Ltd. All rights reserved.